Leucine-rich repeat and calponin homology domain-containing protein 4 (Lrch4) is a single-spanning transmembrane protein that is encoded by the Lrch4 gene in humans. The human form of Lrch4 is 83% identical to murine Lrch4 and was identified in a proteomic screen of macrophage as being rapidly recruited to lipid rafts after LPS exposure. It is predicted to have 680 amino acids and have a molecular weight of 73 kDa.
Toll-like receptors (TLRs) are a type of pattern recognition receptors found in vertebrates and invertebrates—there are ten different varieties in humans all of which recognize different ligands. TLRs 1, 2, 4, 5, and 6 are expressed as cell surface receptors, while TLRs 3, 7 and 9 are expressed on internal cellular membranes. TLRs are categorized as pattern recognition receptors because they recognize conserved aspects microbial proteins, such as bacterial cell-surface lipopolysaccharides, or in the case of intracellular receptors, foreign nucleic acids. Not surprisingly, they play a central role in the innate immune response and are known to be involved in signaling pathways that control cytokine production. TLRs commonly function as dimers. While most TLRs appear to function as homodimers, TLR2 is known to form heterodimers with TLR1 and TLR6, although each of these dimers has a different ligand specificity. Cell signaling mediated by all TLRs other than TLR3 involves interacting with the accessory protein MyD88, a cytosolic adaptor which is known to activate the transcription factor NF-κB.
In addition, and in some instances because of, their role in innate immunity, TLRs are also known (or implicated) to play a significant role in certain diseases, such as sepsis; respiratory diseases (acute respiratory distress syndrome, asthma, and chronic obstructive pulmonary disease); autoimmune diseases (systemic lupus erythematosus and rheumatoid arthritis); inflammatory bowel syndrome; heart disease (acute coronary syndrome); cancer; metabolic syndrome; and atherosclerosis, to name a few. Because of the association of TLRs with disease, they are an attractive target for new therapeutics. See Hennessy et al., Nature Reviews 9:293 (2010).